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1.
Antioxidants (Basel) ; 12(6)2023 May 26.
Article in English | MEDLINE | ID: mdl-37371887

ABSTRACT

Total bilirubin consists of an unconjugated form, solubilized by its binding to albumin, and a conjugated form representing a minor part of the circulating bilirubin. As total bilirubin in physiological concentrations is a powerful antioxidant, its concentration gradient may reflect the health status of an individual, and serve as a prognostic indicator of outcome in primary and secondary cardiovascular disease prevention. The aim of this study was to assess the association between total bilirubin and incident cardiovascular events following a myocardial infarction. Total bilirubin in serum was measured at baseline 2-8 weeks after hospitalization for an MI in 881 patients, aged 70 to 82 years, included in the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) study, where patients were followed-up for up to 2 years. The first major adverse clinical event (MACE) was the primary endpoint and consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. As total bilirubin was non-normally distributed, log-transformed values and quartiles of bilirubin were analyzed using Cox regression models. The median (Q1, and Q3) baseline concentration of bilirubin was 11 (9, and 14) µmol/L, and higher log-transformed concentrations were associated with male sex, lower New York Heart Association (NYHA) class and non-smoking. MACE occurred in 177 (20.1%) patients during the follow-up. Higher concentrations of bilirubin were associated with a lower risk of MACE: HR 0.67 (95%CI 0.47-0.97) per log-unit increase, p = 0.032. Patients in the lowest quartile of bilirubin (<9 µmol/L) had the highest risk with HR 1.61 (95%CI 1.19-2.18), p = 0.002, compared to quartiles 2-4. This association remained significant even after adjusting for age, sex, body mass index (BMI), smoking status, NYHA class and treatment allocation: HR 1.52 (1.21-2.09), p = 0.009. Low concentrations of bilirubin (<9 µmol/L) are associated with increased nonfatal cardiovascular events or death in elderly patients with a recent myocardial infarction.

2.
Circulation ; 143(6): 528-539, 2021 02 09.
Article in English | MEDLINE | ID: mdl-33191772

ABSTRACT

BACKGROUND: High intake of marine n-3 polyunsaturated fatty acids (PUFA) has been associated with reduced risk of cardiovascular events; however, this has not been confirmed in patients with a recent acute myocardial infarction (AMI). Elderly patients are at particularly increased cardiovascular risk after myocardial infarction, but few trials address this group specifically. Omega-3 fatty acids hold the potential to reduce cardiovascular events with limited adverse effects in this vulnerable group. The hypothesis was that daily addition of 1.8g n-3 PUFA to standard of care secondary prophylaxis in elderly patients who have survived an AMI would reduce the risk of subsequent cardiovascular events during 2 years follow-up. METHODS: The OMEMI trial (Omega-3 Fatty acids in Elderly with Myocardial Infarction) is an investigator-initiated, multicenter, randomized clinical trial adding 1.8 g n-3 PUFA (930 mg eicosapentaenoic acid and 660 mg docosohexaenoic acid) versus placebo (corn oil) daily to standard of care in patients aged 70 to 82 years with recent (2-8 weeks) AMI. The primary endpoint was a composite of nonfatal AMI, unscheduled revascularization, stroke, all-cause death, heart failure hospitalization after 2 years. The secondary outcome was new atrial fibrillation. The safety outcome was major bleeding. Serum fatty acids were measured as biomarkers of adherence. RESULTS: In total, 1027 patients were randomized. Follow-up data were available for 1014 patients who were included in the intention-to-treat analysis. Mean±SD age was 75±3.6 years, 294 (29%) were female, and mean triglycerides were 111.4±61.9 mg/dL. The primary endpoint occurred in 108 (21.4%) patients on n-3 PUFA versus 102 (20.0%) on placebo (hazard ratio, 1.08 [95% CI, 0.82-1.41]; P=0.60). The secondary endpoint occurred in 28 (7.2%) patients on n-3 PUFA versus 15 (4.0%) on placebo (1.84 [0.98-3.45]; P=0.06). Median changes in eicosapentaenoic acid and docosahexaenoic acid were +87% and +16% for n-3 PUFA versus -13% and -8% for placebo. Major bleeding occurred in 54 (10.7%) and 56 (11.0%) in the n-3 PUFA and placebo groups, respectively (P=0.87). Similar results were found in per-protocol analysis (n=893). CONCLUSIONS: We could not detect reduction in clinical events in our elderly patients with recent AMI who were treated with 1.8 g n-3 PUFAs daily for 2 years. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01841944.


Subject(s)
Fatty Acids, Omega-3/therapeutic use , Myocardial Infarction/drug therapy , Aged , Aged, 80 and over , Fatty Acids, Omega-3/pharmacology , Female , Humans , Male
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